Title : Chrysin attenuates the oxidative stress and neuronal apoptosis related to the reductions of hippocampal neurogenesis in D-galactose-induced brain aging
Abstract:
Brain aging is related to oxidative stress that leads to neuronal apoptosis and cognitive dysfunction. Neurogenesis occurs throughout the lifespan in the subgranular zone of the hippocampal dentate gyrus and it is gradually reduced in brain aging. Long term administration of D-galactose induces oxidative stress, a main factor of neuronal apoptosis resulting in brain aging. Chrysin, a natural flavonoid found in honey, propolis, passion flowers, and mushrooms, has antioxidant properties and protects against neuronal apoptosis in the brain. This study investigated the effects of chrysin on hippocampal neurogenesis through antioxidant and apoptotic pathways in D-galactose-induced brain aging in a rat model. Twelve weeks old male Sprague Dawley rats were divided into 4 groups. The vehicle group received propylene glycol and normal saline. The D-galactose group received intraperitoneal injection of 50 mg/kg of D-galactose. The chrysin group orally received 10 mg/kg of chrysin. The cotreatment group received D-galactose and chrysin at the same doses as the D-galactose and chysin groups. For the first 3 days, all animals received intraperitoneal injection of BrdU 100 mg/kg. After 8 weeks of daily treatment, levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), and apoptotic (Bax and caspase-3) protein expressions in hippocampi were determined. Furthermore, the brain sections were performed to detect cell cycle arrest and neuronal survival using p21 and BrdU/NeuN staining, respectively. The results showed that cotreatment with chrysin decreased MDA levels and improved the activities of SOD, CAT, and GPX. Cotreatment with chrysin downregulated Bax and caspase-3 expressions. Additionally, chrysin diminished the increased p21-positive cells and the reduction of BrdU/NeuN-positive cells caused by D-galactose-induced brain aging. These finding demonstrated that supplementary chrysin possibly attenuated D-galactose-induced brain aging via enhancing the scavenging enzyme activities and neuronal survival. Chrysin also supressed oxidative stress, apoptosis, and cell cycle arrest.
Acknowledgement: This research project is supported by National Research Council of Thailand (NRCT): N41A650079.
Audience Take Away
- This study found that intraperitoneal injection of 50 mg/kg of D-galactose induces oxidative stress and neuronal apoptosis which corresponds to the process of brain aging
- We also found that the D-galactose induces the depletions of hippocampal neurogenesis including cell cycle arrest and reduced neuronal survival
- To expand the results of this study, other faculties may create extracted chrysin from natural products including honey, propolis, passion flowers, or mushrooms to produce new products for treating age-related cognitive impairment
